Quantitative structure activity concentrations

The fundamental assumption of SAR and QSAR (Structure-Activity Relationships and Quantitative Structure-Activity Relationships) is that the activity of a compound is related to its structural and/or physicochemical properties. In a classic article Corwin Hansch formulated Eq. (15) as a linear frcc-cncrgy related model for the biological activity (e.g.. toxicity) of a group of congeneric chemicals [37, in which the inverse of C, the concentration effect of the toxicant, is related to a hy-drophobidty term, FI, an electronic term, a (the Hammett substituent constant). Stcric terms can be added to this equation (typically Taft s steric parameter, E,). 

Schaper, K.-J. QSPRs for vapour pressure and concentration of chemicals above saturated aqueous solutions. In Abstracts of 12th International Workshop on Quantitative Structure-Activity Relationships in Environmental Toxicology, Lyon, Erance, 2006, p. 91. 

Aleksic et al. [47] estimated the hydrophobicity of miconazole and other antimycotic drugs by a planar chromatographic method. The retention behavior of the drugs have been determined by TLC by using the binary mobile phases acetone-n-hexane, methanol toluene, and methyl ethyl ketone toluene containing different amounts of organic modifier. Hydrophobicity was established from the linear relationships between the solute RM values and the concentration of organic modifier. Calculated values of RMO and CO were considered for application in quantitative structure activity relationship studies of the antimycotics. 

The determination of the bioconcentration factor (BCF) can be performed in two different ways computationally with quantitative structure activity relationship (QSAR) methods, or from experimental measurements [2], The QSAR methods estimate BCF from the structural or physicochemical properties of the compound, whereas the experimental methods use measured values of uptake and elimination rate constants or concentrations in the steady state. 

Karcher, W., Devillers, J. (Eds.) Practical Applications of Quantitative Structure-Activity Relationships (QSAR) in Environmental Chemistry and Toxicology, Kluwer Academic Publishers, Dordrecht, 1990 Lieth, H., Markert, B. (Eds.) Element Concentration Cadasters in Ecosystems - Methods of Assessment and Evaluation, VCH, Weinheim, 1990... 

Toxicity is measured by the concentration in mg liter-1 of a compound that causes the death of a certain percentage (usually 50 or 100%) of the test population of a chosen organism (e.g., silvery minnows) in a chosen time (e.g., 96 hours). For organic inhibitors, the higher the concentration needed to achieve a lethal dose of 50%, the less toxic the inhibitor. In Table 12.3 the actual lethal concentration (LC50) (at 96 hr) is compared with that calculated by means of a quantitative structure-activity relation (QSAR). The basic calculation is that of the distribution coefficient of the inhibition of the primary alcohol octanol. 

Linear and non-linear correlations of structural parameters and strain energies with various molecular properties have been used for the design of new compounds with specific properties and for the interpretation of structures, spectra and stabilities 661. Quantitative structure-activity relationships (QSAR) have been used in drug design for over 30 years 2881 and extensions that include information on electronic features as a third dimension (the electron topological approach, ET) have been developed and tested 481 (see Section 2.3.5). Correlations that are used in the areas of electron transfer, ligand field properties, IR, NMR and EPR spectroscopy are discussed in various other Chapters. Here, we will concentrate on quantitative structure-property relationships (QSPR) that involve complex stabilities 124 289-2911. 

Common unspecific mode of action of all organic compounds has been taken up in quantitative structure-activity relationships (QSARs see Chapter 5) as the concept of baseline toxicity and in toxicokinetics as the body burden concept (see Chapter 2). Baseline toxicity refers to the idea that a minimum toxicity expectation may be formulated for any given organic compound based on considerations of a compound s partition properties between hydrophilic and lipophilic chemicals (e.g., between water and octanol). Commonly, this is expressed in terms of the octanol-water partition coefficient (K0,J of a chemical. The partition coefficient allows estimations of a local concentration or body burden for each individual chemical in the mixture. Assuming that this produces the same toxic effect (disturbances of cell membranes), it is then possible to anticipate joint narcotic action by adding together the respective local concentrations or body burdens for each individual mixture component. 

Abstract Quantitative structure-activity relationship (QSAR) analysis for minimum inhibitory concentration (MIC) of phenothiazines and benzo[a]phenothiazines was investigated based on the theoretical calculations. Four different dipole moments (/jq, /xesp g, /zw, and /zesp-w) and heats of formation (AHf) of the phenothiazines [1-20], benzo [n]phenothiazines [21-29], and benz[c]acridines [30-41] were separately calculated in the gas-phase and the water-solution by the conductor-like screening model/parametric method 3 (COSMO/PM3) technique. The MIC values of phenothiazines [1-20] were well correlated to A AHf, HOMO energy and hq. QSAR may be applicable to predict the MIC of phenothiazines. 

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